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Updated: Apr 3, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Targeted therapies in bladder cancer: an overview of in vivo research
Kim E M van Kessel1, Tahlita C M Zuiverloon2, Arnout R Alberts2
1Department of Pathology, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, Netherlands.
Abstract:
Survival of patients with muscle-invasive bladder cancer is poor and new therapies are needed. Currently, none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer and the few clinical trials that have been performed had limited success, often owing to a lack of efficacy and toxic effects. However, many other novel targeted agents have been investigated in animal models of bladder cancer. EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 are molecular targets that could be efficiently inhibited, resulting in reduced tumour growth, and that have been investigated in multiple independent studies. Several other targets, for example COX-2, IL-12, Bcl-xL, livin and choline kinase α, have also been observed to inhibit tumour growth, but these findings have not been replicated to date. Limitations of several studies include the use of cell lines with mutations downstream of the target, providing resistance to the tested therapy. Furthermore, certain technologies, such as interfering RNAs, although effective in vitro, are not yet ready for clinical applications. Further preclinical research is needed to discover and evaluate other possible targets, but several validated targets are now available to be studied in clinical trials.
Insights
New targeted therapies are crucial for muscle-invasive bladder cancer. Several molecular targets show promise in preclinical studies, offering potential for future clinical trials and improved patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Muscle-invasive bladder cancer (MIBC) has a poor prognosis, necessitating novel therapeutic strategies.
- Current targeted therapies approved for other cancers have shown limited success in MIBC clinical trials due to efficacy and toxicity issues.
Purpose of the Study:
- To review potential molecular targets for novel targeted therapies in muscle-invasive bladder cancer.
- To evaluate the preclinical evidence for various molecular targets investigated in MIBC animal models.
Main Methods:
- Review of preclinical studies investigating targeted agents against molecular targets in MIBC.
- Analysis of molecular targets such as EGFR, FGFR-3, VEGF, mTOR, STAT3, androgen receptor, and CD24.
- Consideration of other investigated targets including COX-2, IL-12, Bcl-xL, livin, and choline kinase α.
Main Results:
- Multiple molecular targets (EGFR, FGFR-3, VEGF, mTOR, STAT3, androgen receptor, CD24) have demonstrated tumor growth inhibition in preclinical MIBC models.
- Some targets (e.g., COX-2, IL-12) have shown inhibitory effects, but findings require replication.
- Limitations identified include the use of resistant cell lines and the immaturity of certain technologies (e.g., interfering RNAs) for clinical use.
Conclusions:
- Several validated molecular targets are available for investigation in future clinical trials for muscle-invasive bladder cancer.
- Further preclinical research is essential to discover and validate additional therapeutic targets.
- Advancing targeted therapy development is critical to improve survival rates for MIBC patients.
